Structural studies on technetium coordination ability of cysteine-containing peptides

In ^99mTc labelling of specific peptides, ^99mTc has to be introduced at a position of the peptide molecule which would tolerate inclusion of the label without adversely affection the receptor or other specific binding. Although for direct labelling of peptides Tc-binding sequences remote from the receptor-binding sequence have been successfully introduced, the corrdination mode of such peptides is still poorly understood. The aim of our studies was I) to clarify for simple N,S-donor building blocks, such as cysteine derivatives, how the ligands bind Tc(V) and II) to determine in solution the coordination mode of a ⁹⁹Tc-labelled endothelin derivative, containing the sequence -Cys-Gly-Cys-, which is a potential agent for imaging atherosclerosis. X-ray asorption spectroscopy proved to be a valuable tool in obtaining direct structural information from the noncrystalline material and solution species. The performed studies have shed more light on the subtle interplay of the donor groups of the ligand, including the hitherto uncommon occurrence of both a deprotonated and a neutral nitrogen donor group in bis-bidentate S,N oxometal(V) complexes. EXAFS analysis of the ⁹⁹Tc-labelled Cys-containing endothelin derivative revealed that coordination of the [TcO]³⁺ core is restricted to the sequence -Cys-Gly-Cys-. Under the labelling condition used (ligand exchange reaction with Tc(V) gluconate), the preferred coordination by the cysteinyl thiol group surprisingly prevents involvement of any donor atom other than sulphur, thus forming purely S-coordinate 1:2 complexes in form of two isomers.